Gene expression analysis of MAOA and the clock gene ARNTL in individuals with bipolar disorder compared to healthy controls

Abstract

Introduction

Circadian rhythms are associated with bipolar disorder (BD). This cross-sectional study aimed at investigating ARNTL and MAOA gene expression differences (1) between individuals with BD and controls, (2) between affective episodes, and (3) the relationship between ARNTL and MAOA expression.

Methods

ARNTL and MAOA gene expression in peripheral mononuclear blood cells were analysed from fasting blood samples (BD n =  81, controls n = 54) with quantitative real-time PCR operating on TaqMan® assays (normalised to 18S RNA expression). ANCOVAs corrected for age, sex, body mass index, and medication was used to evaluate expression differences and correlation analyses for the relation between ARNTL and MAOA expression.

Results

ARNTL gene expression differed between affective episodes (F(2,78) = 3.198, p = 0.047, Partial Eta²= 0.083), but not between BD and controls (n.s.). ARNTL and MAOA expression correlated positively in BD (r = 0.704, p < 0.001) and in controls (r = 0.932, p < 0.001). MAOA expression differed neither between BD and controls nor between affective episodes (n.s.).

Discussion

Clock gene expression changes were observed in different affective states of BD. More precisely, ARNTL gene expression was significantly higher in euthymia than in depression. ARNTL and MAOA gene expression correlated significantly in BD and in controls, which emphasises the strong concatenation between circadian rhythms and neurotransmitter breakdown.

Keywords:

• Bipolar disorder
• clock genes
• ARNTL
• MAOA

Acknowledgement

Furthermore, we thank all study participants for investing their time to participate in this study. Furthermore, we thank all colleagues from the Medical University of Graz and KAGES, as well as friends and family who supported us over the years. Special thanks for the funding by ‘MEFO Graz, Gesundheit 3000’, ‘STADT Graz’ and ‘Franz-Lanyar’ (project ‘Is the molecular clock ticking differently in Bipolar Disorder’). Furthermore, I especially thank the native speaker Lara Murphy for proofreading.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This was supported by Franz Lanyar Stiftung.